Unit 2, Topic 1—To Do List	Suggested Average Time to Complete (min)
Read, make summary notes, and complete the self-check questions for Unit 2, Topic 1 of TRU Cell and Molecular Biology.	60
Complete Learning Activity: Fluid Mosaic Model.	15
Complete Learning Activity: Gorter and Grendal experiment.	15
Complete Learning Activity: Membrane Fluidity.	45
Complete Learning Activity: Micelle Formation.	30

Lipid Bilayers

The protective membrane around cells contains many components, including cholesterol, proteins, glycolipids, phospholipids, and sphingolipids. The last two of these will, when mixed vigorously with water, spontaneously form what is called a lipid bilayer, which serves as a protective boundary for the cell that is largely impermeable to the movement of most materials across it. With the notable exceptions of water, carbon dioxide, carbon monoxide, and oxygen, most polar/ionic molecules require transport proteins to help them navigate across the bilayer.

The orderly movement of these compounds is critical for the cell to be able to:

• Obtain food for energy
• Export materials
• Maintain osmotic balance
• Create gradients for transport
• Provide electromotive force for nerve signalling,
• Store energy in electrochemical gradients for ATP production (oxidative phosphorylation or photosynthesis).

Though some cells do not have cell walls (animal cells) and others do (bacteria, fungi, and plants), all cells possess plasma membranes. All plasma membranes have a lipid bilayer, each containing a significant number of amphiphilic molecules, including phospholipids and sphingolipids.

Components of Lipid Bilayers

Fatty acids

Unlike monosaccharides, nucleotides, and amino acids, fatty acids are not monomers linked together to form much larger molecules. Although fatty acids can link together (e.g., into triacylglycerols or phospholipids), they are not linked directly to one another, and there are generally no more than three in a given molecule. The fatty acids themselves are long chains of carbon atoms topped off with a carboxyl group. The chain length can vary, although most are between 14 and 20 carbons, and in higher-order plants and animals, fatty acids with 16 and 18 carbons are the major species.

 

Due to the synthesis mechanism, most fatty acids have an even number of carbons, although odd-numbered carbon chains are possible. Double bonds between the carbons can generate more variety. Fatty acid chains with no double bonds are saturated because each carbon bonds to as many hydrogen atoms as chemically possible. Fatty acid chains with double or triple bonds are unsaturated (Figure 1). Those with more than one double or triple bond are called polyunsaturated. The fatty acids in eukaryotic cells contain nearly even amounts of saturated and unsaturated types; many of the latter may be polyunsaturated (Table 1).

Table 1: Common fatty acids and their carbon chain length and number of C-C double bonds. (Adapted from Katzman et al. 2020/Fundamentals of Cell Biology) CC BY-NC-SA 4.0
Fatty Acid	Number of carbon atoms : Number of C-C double bonds
Myristic Acid	14:0 (14 carbons, no C-C double bonds)
Palmitic Acid	16:0
Stearic Acid	18:0
Arachidic Acid	20:0
Palmitoleic Acid	16:1
Oleic Acid	18:1
Linoleic Acid	18:2
Arachidonic Acid	20:4

There are significant physical differences between the saturated and unsaturated fatty acids simply due to the geometry of the double-bonded carbons. A saturated fatty acid is very flexible, with free rotation around all its C-C bonds. The usual linear diagrams and formulas depicting saturated fatty acids also explain the ability of saturated fatty acids to pack tightly together with very little intervening space. On the other hand, unsaturated fatty acids cannot pack as tightly because of the rotational constraint imposed by the double bond. The carbons cannot rotate around the double bond, which forms a “kink” in the chain.

Phospholipids

Phospholipids (also called phosphoglycerides or glycerophospholipids) are fatty acids attached to glycerol. However, instead of three fatty acid tails, there are only two, and a phosphate group is attached to the third carbon of the glycerol molecule (Figure 2). The phosphate group also links to a “head group.” The identity of the head group and the fatty acid tails name the molecule. Phospholipids are amphipathic. Amphipathic means that a structure is hydrophobic on one end and hydrophilic on the other. The fatty acid tails in a phospholipid are highly hydrophobic, while the head group is highly hydrophilic. The amphipathic nature of phospholipids plays a crucial part in their role as the primary component of cellular membranes.

 

Sphingolipids (Figure 3 and Figure 4) are also important constituents of membranes. Instead of a glycerol backbone, their base is the amino alcohol, sphingosine (or dihydrosphingosine). There are four major types of sphingolipids: ceramides, sphingomyelins, cerebrosides, and gangliosides. Ceramides are sphingosine molecules with a fatty acid tail attached to the amino group. Sphingomyelins are ceramides in which a phosphocholine or phosphoethanolamine attaches to the 1-carbon. Cerebrosides and gangliosides are glycolipids with a single monosaccharide or multiple saccharides attached to the 1-carbon of a ceramide, respectively. The oligosaccharides attached to gangliosides all contain at least one sialic acid residue. In addition to being a structural component of the cell membrane,gangliosides play an important role in cell-to-cell recognition.

 

 

In each case, the phospholipid or sphingolipid has one polar and one nonpolar end. These amphiphilic molecules arrange themselves similarly to amino acids that tend to have their hydrophobic side chains on the inside of a folded protein to exclude water. This tendency of molecules, including proteins and phospholipid bilayers, to hide their hydrophobic regions is known as the hydrophobic effect. Remember that the cytoplasm of a cell contains a high percentage of water, and the exterior of the cell is also aqueous. It, therefore, makes perfect sense that the polar portions of the membrane molecules arrange themselves as they do — polar parts outside interacting with water and nonpolar parts in the middle of the bilayer avoiding/excluding water (Figure 5).

 

Folding of the Phospholipid Bilayer

Since most cells live in an aqueous environment and cell contents are mostly aqueous, it makes sense that a membrane that separates one side from the other must be hydrophobic to form an effective barrier against accidental leakage of materials or water. Cellular membranes are composed primarily of phospholipids. Phospholipids are molecules consisting of a phosphorylated polar head group attached to a glycerol backbone with two long hydrocarbon tails. The composition of the hydrocarbons varies in length, degree of saturation, and head group.

Because the phospholipids are amphipathic, the expected simplest conformation for a small group of phospholipids in an aqueous solution might be a micelle (Figure 6A), but is this the case? Mixtures of hydrophobic molecules and water are thermodynamically unstable, so a micelle would protect the hydrophobic fatty acid tails from the aqueous environment with which the head groups interact. Micelles can form with other amphipathic lipids, the most recognizable being detergents, like sodium dodecyl sulfate (SDS) (also called sodium lauryl sulfate), used in common household products, such as shampoos. Detergents surround hydrophobic dirt (Figure 6B) and hold it in solution within the micelle for water to rinse it away. At smaller sizes, the micelle is fairly stable; however, when there are a large number of phospholipids, the space inside the micelle becomes larger and can trap water in direct contact with the hydrophobic tails (Figure 6C), rendering the micelle unstable. Therefore, a single large phospholipid layer is unlikely to be stable enough to act as a biological membrane.

Additionally, micelles form easily with SDS and other single-tailed lipids because their overall shape (van der Waals envelope) is conical (Figure 6D), which lends itself to fitting tight curvatures. However, phospholipids are more cylindrical, which makes it harder to fit them into a tight spherical micelle. If they do form micelles, they tend to be larger and are likely to collapse.

On the other hand, a phospholipid bilayer (Figure 7A) could form a fatty acid sandwich in which the polar head groups face outward to interact with an aqueous environment and the sequestered fatty acids in between. However, this does not resolve the problem on the edges of the sandwich. Therefore, the solution to the ideal phospholipid structure in an aqueous environment is a spherical phospholipid bilayer (Figure 7B and cutaway in Figure 7C): no edges mean no exposed hydrophobicity.

 

The stability of the spherical phospholipid bilayer does not imply that it is static in its physical properties. In most physiologically relevant conditions, the membrane is cohesive but fluid. It can mould its surface to the contours of whatever it is resting on, and the same thermodynamic and hydrophobic properties that make it so stable allow it to spontaneously seal up minor tears.

Composition Bias

The composition of plasma membranes is different depending on their location. First, glycosylation (of lipids and proteins) has the sugar groups located almost exclusively on the outside of the cell, away from the cytoplasm (Figure 8 and Figure 9). Among the membrane lipids, sphingolipids are much more commonly glycosylated than phospholipids. Additionally, different types of phospholipids can be found preferentially on one side of the membrane or the other. Phosphatidylserine and phosphatidylethanolamine are found preferentially within the inner leaflet (side) of the plasma membrane, whereas phosphatidylcholine tend to be located on the outer leaflet. Notably, in the process of apoptosis, phosphatidylserines flip to the outer leaflet, where they serve as a signal to macrophages to bind and destroy the cell. Sphingolipids are found preferentially in the plasma membrane and are almost completely absent from mitochondrial and endoplasmic reticulum membranes.

 

Diffusion of Lipids Within the Membrane

Lateral Diffusion

The movement of lipids within each leaflet (side) of the lipid bilayer occurs readily and rapidly due to membrane fluidity. This type of movement is called lateral diffusion and can be measured by a technique called fluorescence recovery after photobleaching (FRAP) (Figure 10). In this method, a laser strikes and stains a section of the lipid bilayer of a cell, leaving a spot (shown in Figure 10B). Over time, the stain ultimately diffuses across the entire lipid bilayer, like a drop of ink added to a glass of water. A measurement of the diffusion rate indicates the fluidity of a membrane.

 

Transverse Diffusion

While the movement in lateral diffusion occurs rapidly, the movement of lipids from one leaflet over to the other occurs much more slowly or not at all. This type of molecular movement is called transverse diffusion and is almost nonexistent in the absence of enzyme action. Remember that there is a molecule distribution bias between membrane leaflets, which means that something must be organizing them.

Three enzymes catalyze the movement of compounds in transverse diffusion (Figure 11). Flippases move membrane glycerophospholipids/sphingolipids from the outer leaflet (extracellular space) to the inner leaflet (cytoplasmic side) of the cell. Floppases move membrane lipids in the opposite direction. Scramblases move them in either direction.

Other Components of the Lipid Bilayer

Besides phospholipids and sphingolipids, the lipid bilayer of cellular membranes commonly contains other materials. Two important and prominent ones are cholesterol (Figure 12) and proteins. Cholesterol is a saturated hydrocarbon consisting of four fused rings; the flatness and hydrophobicity of the sterol rings allow cholesterol to interact with the nonpolar portions of the lipid bilayer. In contrast, the hydroxyl group can interact with the hydrophilic part (Figure 13).

Membrane Fluidity

In 1972, S. J. Singer and Garth L. Nicolson proposed a new plasma membrane model that, compared to earlier understanding, better explained microscopic observations and the function of the plasma membrane. This model is called the fluid mosaic model. The model has somewhat evolved over time, but it still provides the best illustration of the plasma membrane structure and functions as we now understand it. The fluid mosaic model describes the structure of the plasma membrane as a mosaic of components — including phospholipids, cholesterol, proteins, and carbohydrates — in which the components can flow and change position while maintaining the basic integrity of the membrane. Both phospholipid molecules and embedded proteins can diffuse rapidly and laterally in the membrane. The fluidity of the plasma membrane is necessary for the activities of certain enzymes and transport molecules within the membrane. Plasma membranes range from 5–10 nm thick. As a comparison, human red blood cells, visible via light microscopy, are approximately 8-µm thick, or approximately 1,000 times thicker than a plasma membrane.

Maintaining a working range of fluidity is important to the cell. If the membrane is too rigid, then it may be unable to move or undergo necessary processes such as endocytosis, in which a cell takes up large extracellular molecules by enveloping them with the cell membrane and pinching them off in a vesicle. On the other hand, if it becomes too fluid, it may fall apart. Although some phospholipids directly link to proteins and the cytoskeleton, most are not; therefore, they are free to move within the plane of their layer in the bilayer.

The following three major factors govern the fluidity of the plasma membrane:

• The degree of saturation and length of the fatty acid chains
• Temperature
• Cholesterol concentration

Because fully saturated fatty acid chains have no “kinks,” they can pack together very tightly, decreasing membrane fluidity. As more unsaturated fatty acid chains are added to the membrane, the kinks in their chains create more space between some of the fatty acid tails, increasing fluidity. Therefore, a membrane with more saturated fatty acid chains will have a more solid-like membrane, while a membrane with more unsaturated fatty acid chains will be more fluid-like. Similarly, at higher temperatures, even saturated fatty acid chains, with their increased energy, move more and create more space between the chains, increasing fluidity.

Finally, the structure of cholesterol is fantastic in that it allows both an increase and a decrease in membrane fluidity. Its ring structure is rigid (not freely rotatable), causing a reduction in molecular motion and decreasing membrane fluidity. However, the rings are also bulky, which increases the space around the cholesterol and allows for greater movement of neighbouring fatty acid chains; all these factors increase in membrane fluidity. The ability of cholesterol to increase and decrease fluidity is similar to a “buffer” for the membrane fluidity that helps prevent the membrane from becoming too fluid-like or solid-like.

Cholesterol’s influence on membrane fluidity is complex. Figure 14 shows the phase transition for a membrane as it is heated, moving from a more “frozen” state to a more “fluid” one as the temperature rises. The mid-point of this transition, referred to as the Tm, is influenced by the fatty acid composition of the lipid bilayer compounds. Longer and more saturated fatty acids will favour higher Tm values, whereas unsaturation and short fatty acids will favour lower Tm values. This preference is why fish, which live in cool environments, have a higher level of unsaturated fatty acids; they use them to make membrane lipids that remain fluid at ocean temperatures. Interestingly, cholesterol does not change the Tm value but instead widens the transition range between frozen and fluid forms of the membrane, allowing it to have a wider range of fluidity.

In addition to the three factors noted above, phospholipid composition can also alter membrane fluidity: shorter acid chains lead to greater fluidity. In comparison, longer chains, with more surface area for interaction, generate membranes with higher viscosity. The phospholipid composition of biological membranes is dynamic and varies widely. In Figure 15, the structures of the major phospholipid species phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), and sphingomyelin (SM) in plasma membranes from two different cell types. Due to their differing functions, the ratios of plasma membrane lipids of a myelinating Schwann cell are very different from lipids in the plasma membrane of a red blood cell.

 

However, some similarities exist between most eukaryotic membranes, such as the major component (~50%) phosphatidylcholine (PC) (Figure 16). Phosphatidylcholine structure consists of a choline molecule attached to the phosphate in the phospholipid structure. The fatty acid tails have one straight saturated and one bent unsaturated fatty acid. This bend generates space in the membrane and, therefore, increases fluidity. As the major component of most eukaryotic membranes, it ensures the overall ability of the membrane to maintain its structure and semi-permeable properties.

 

In addition, the mosaic characteristic of the membrane helps the plasma membrane remain fluid (Figure 17). The integral proteins and lipids exist in the membrane as separate but loosely attached molecules. The membrane is not like a balloon that can expand and contract; instead, it is fairly rigid and can burst if penetrated or if a cell takes in too much water. However, its mosaic nature means a very fine needle can easily penetrate a plasma membrane without causing it to burst; the membrane will flow and self-seal upon removal of the needle.

 

Unlike eukaryotes, bacterial membranes (with some exceptions, e.g., Mycoplasma and methanotrophs) generally do not contain sterols. However, many microbes contain structurally related compounds called hopanoids that likely fulfill the same function. Unlike eukaryotes, bacteria can have a wide variety of fatty acids within their membranes. Along with typical saturated and unsaturated fatty acids, bacteria can contain fatty acids with additional methyl, hydroxy or even cyclic groups. The bacterium can modulate the relative proportions of these fatty acids to maintain the optimum fluidity of the membrane (e.g., following temperature change).

Lipid Rafts

Even within a single cell, the composition of the plasma membrane differs from that of intracellular organelles. Heterogeneity exists even within a membrane itself — the lipids are not distributed randomly in the membrane. Over the last two decades, research has identified lipid “rafts” that appear to have a specific role in embedding particular proteins. Since they are unanchored lipids, the rafts can move laterally within the membrane, just like most individual lipid molecules. Finally, the two layers of the bilayer have different ratios of the lipids. The cytoplasmic face of every membrane will have different associations and functions than the extracellular face.

In broad terms, the rafts are considered small areas of ordered lipids within a larger undirected membrane. A distinguishing feature of the rafts is that they are more ordered than the bilayer surrounding them; they contain more saturated fatty acids (tighter packing and less disorganization, as a result) and up to five times as much cholesterol as the bilayer (Figure 18). Additionally, they are relatively rich in sphingolipids, with as much as 50% greater quantities of sphingomyelin than surrounding areas of the bilayer. The higher cholesterol concentration in the rafts may be due to its greater ability to associate with sphingolipids (Figure 18).

Lipid rafts most often form in association with specific membrane proteins while excluding others. Usually, the included proteins have signalling-related functions, and one model proposes that these proteins may direct the organization of selected lipids around them rather than the other way around. Lipid rafts affect membrane fluidity, neurotransmission, and trafficking of receptors and membrane proteins.

 

Membrane Proteins

Proteins make up the second major component of plasma membranes. Proteins in a lipid bilayer can vary in quantity enormously, depending on the membrane. Protein content by weight of various membranes typically ranges between 30% and 75% by weight. Some mitochondrial membranes can have up to 90% protein. Proteins linked to and associated with membranes come in several types. There are two main categories of membrane proteins: integral and peripheral.

Before discussing membrane proteins, it is important to review protein structure and predict what chemical properties would allow them to associate with a cell membrane.

Transmembrane Proteins

Transmembrane proteins are integral membrane proteins that span from one side of a biological membrane to the other and are firmly embedded in the membrane (Figure 20). Transmembrane proteins can function as docking sites for attachment (e.g., to the extracellular matrix), as receptors in the cellular signalling system, or facilitate the specific transport of molecules into or out of the cell (see Evolution Connection below).

 

As their name suggests, integral proteins (some specialized types are called integrins) integrate completely into the membrane structure, and their hydrophobic membrane-spanning regions interact with the hydrophobic region of the phospholipid bilayer (Figure 21). Single-pass integral membrane proteins usually have a hydrophobic transmembrane segment with 20 to 25 amino acids. Some span only part of the membrane — associating with a single layer — while others stretch from one side of the membrane to the other with either side exposed. Some complex proteins are composed of up to 12 segments of a single protein, which are extensively folded and embedded in the membrane. This type of protein has a hydrophilic region or regions and one or several mildly hydrophobic regions. This region arrangement of the protein tends to orient the protein alongside the phospholipids, with the hydrophobic region of the protein adjacent to the tails of the phospholipids and the hydrophilic region or regions of the protein protruding from the membrane and in contact with the cytosol or extracellular fluid.

In all cases, the portion within the lipid bilayer consists primarily of hydrophobic amino acids. These are usually arranged in an alpha-helix so that the polar -C=O and -NH groups at the peptide bonds can interact with each other rather than with their hydrophobic surroundings. Therefore, integral membrane proteins can only be separated from the membranes using detergents (such as sodium dodecyl sulfate or SDS), nonpolar solvents, or sometimes denaturing agents. The portions of the polypeptide that project out from the bilayer tend to have a high percentage of hydrophilic amino acids. Furthermore, those that project into the aqueous surroundings of the cell are usually glycoproteins, with many hydrophilic sugar residues attached to the part of the polypeptide exposed at the surface of the cell. Some transmembrane proteins that span the bilayer several times form a hydrophilic channel through which certain ions and molecules can enter (or leave) the cell (see Unit 2, Topic 2).

Examples of integrated/transmembrane proteins include those involved in transport (e.g., Na⁺/K⁺ ATPase), ion channels (e.g., potassium channels of nerve cells), and signal transduction across the lipid bilayer (e.g., G-protein-coupled receptors). These will be discussed in further detail later on in this course.

Transmembrane helices are visible in structures of membrane proteins determined by X-ray crystallography. Hydrophobicity scales can also predict them. Because the interior of the bilayer and the interiors of most known protein structures are hydrophobic, amino acids spanning a membrane are presumed to also require hydrophobicity. However, membrane pumps and ion channels also contain numerous charged and polar residues within the generally nonpolar transmembrane segments (see Unit 2, Topic 2 and Unit 2, Topic 3).

In some of these integral membrane proteins, large extracellular and intracellular domains are present and connected by the intramembrane regions. The intramembrane spanning region often consists of either a single alpha-helix or multiple different helical regions, which zig-zag through the membrane. Hydropathy calculations can readily determine these transmembrane sequences. For example, consider the hydropathy plot of the integral membrane bovine protein rhodopsin (Figure 22). The plot has the amino acid sequence of a protein on its x-axis and the degree of hydrophobicity and hydrophilicity on its y-axis. There are several methods to measure the degree of polar solvent interaction, such as water with specific amino acids. Analyzing the shape of the plot gives information about the partial structure of the protein. For instance, if a stretch of about 20 amino acids shows positive for hydrophobicity, these amino acids may be part of an alpha-helix spanning across the lipid bilayer; they would be above the horizontal line shown by the arrow in Figure 22. Conversely, amino acids with high hydrophilicity indicate that these residues are in contact with solvent (e.g., water) and, therefore, likely to reside on the outer surface of the protein. In overall topology, these amino acids would reside in the extracellular or intracellular regions.

 

Integral membrane proteins can be released from the membrane and effectively solubilized by adding single-chain amphiphiles (detergents), which form a mixed micelle with the integral membrane protein. Mixed micelle forms when nonpolar tails in detergents interact with the hydrophobic transmembrane domain in the membrane protein. Studying membrane proteins in a more natural environment can involve reconstituting proteins solubilized by nonionic detergent into bilayer liposome structures. Nonionic detergents (e.g., Triton X-100, octylglucoside) are often used to purify membrane proteins in their natural state. Not only do ionic detergents (like SDS) solubilize integral membrane proteins, but they can also denature them.

Glycocalyx

Carbohydrates are the third major component of plasma membranes. They are always found on the exterior surface of cells and are bound to either proteins (forming glycoproteins) or lipids (forming glycolipids). These carbohydrate chains may consist of two to 60 monosaccharide units and can be either straight or branched. Carbohydrate components of glycosylated membrane proteins inform their function. Along with peripheral proteins, carbohydrates form specialized sites on the cell surface that allow cells to recognise each other. This recognition function is very important to cells, as it allows the immune system to differentiate between body cells (called “self”) and foreign cells or tissues (called “non-self”). Similar types of glycoproteins and glycolipids are found on the surfaces of viruses and may change frequently, preventing immune cells from recognizing and attacking them (see Evolution Connection below). Glycoproteins also enable specific interactions of cells with each other to form tissues.

These carbohydrates on the exterior surface of the cell — the carbohydrate components of both glycoproteins and glycolipids — are collectively referred to as the glycocalyx (meaning “sugar coating”). The glycocalyx is highly hydrophilic and attracts large amounts of water to the surface of the cell. This function aids in the interaction of the cell with its watery environment and its ability to obtain substances dissolved in the water.

Cells have hundreds to thousands of membrane proteins, and the protein composition of a membrane varies with its function and location. Glycoproteins embedded in membranes play important roles in cellular identification. Blood types, for example, differ from each other in the structure of the carbohydrate chains projecting out from the surface of the glycoprotein in their membranes (Figure 23).

 

Peripheral Membrane Proteins

Peripheral membrane proteins are more loosely associated with the membrane and interact with a part of the bilayer (usually not involving hydrophobic interactions) but do not project through it (Figure 20 and Figure 25). Associated membrane proteins typically do not have external hydrophobic regions, so they cannot embed in a portion of the lipid bilayer, and they are usually noncovalently attached to the protruding portions of integral membrane proteins (Figure 20 and Figure 25-4). Such associations may arise from interactions with other proteins or molecules in the lipid bilayer. In contrast to integral membrane proteins, peripheral membrane proteins tend to collect in the water-soluble component or fraction of all the proteins extracted during a protein purification procedure.

Anchored membrane proteins are not embedded in the lipid bilayer; instead, they covalently attach to a molecule (typically a fatty acid) embedded in the membrane (Figure 25-3). These proteins insert themselves and assume a place alongside the similar fatty acid tails in the bilayer structure of the membrane. The lipid-anchored protein can be located on either side of the cell membrane. Thus, the lipid serves to anchor the protein to the cell membrane. Lipid-anchored proteins are covalently attached to different fatty acid acyl chains on the cytoplasmic side of the cell membrane via palmitoylation, myristoylation or prenylation.

On the exoplasmic face of the cell membrane, lipid-anchored proteins covalently attach to the lipids glycosylphosphatidylinositol (GPI) and cholesterol. Glycosylphosphatidylinositol attaches to the C-terminus of a protein during posttranslational modification in the rough endoplasmic reticulum, resulting in a GPI-anchored protein. Phospholipase C (PLC) is an enzyme known to cleave the phospho-glycerol bond found in GPI-anchored proteins. Detergents cannot remove GPI-anchored proteins, so releasing GPI-linked proteins from the outer cell membrane requires treatment with PLC.

 

Membrane proteins are often restricted in their movements. Since a lipid bilayer is a film of oil, the structures immersed in it may be expected to be relatively free to float about. For some membrane proteins, this is the case. For others, however, their mobility is limited as follows:

• Some proteins exposed at the interior face of the plasma membrane are tethered to cytoskeletal elements (e.g., actin microfilaments).
• Some proteins at the exterior face of the plasma membrane are anchored to components of the extracellular matrix (e.g., collagen).
• Integral membrane proteins cannot pass through the tight junctions found between some kinds of cells (e.g., epithelial enterocyte cells).

Key Concepts and Summary

• The modern understanding of the plasma membrane is the fluid mosaic model.
• The plasma membrane is composed of a bilayer of phospholipids, with their hydrophobic, fatty acid tails touching each other.
• Proteins stud the landscape of the membrane, some of which span the membrane.
  • Cells have hundreds to thousands of membrane proteins, and the protein composition of a membrane varies with its function and location; some  proteins transport materials into or out of the cell.
• Carbohydrates are attached to some of the proteins and lipids on the outward-facing surface of the membrane, forming complexes that identify the cell from other cells.
• The fluid nature of the membrane is due to temperature, the configuration of the fatty acid tails (some kinked by double bonds), the presence of cholesterol embedded in the membrane, and the mosaic nature of the proteins and protein-carbohydrate combinations (not firmly fixed in place).
• Plasma membranes enclose and define the borders of cells; rather than being a static bag, they are dynamic and constantly in flux and have the following characteristics, summarized in Table 3:
  • The main fabric of the membrane is composed of amphiphilic or dual-loving phospholipid molecules.
  • Integral proteins, the second major component of plasma membranes, integrate completely into the membrane structure with their hydrophobic membrane-spanning regions interacting with the hydrophobic region of the phospholipid bilayer.
  • Carbohydrates, the third major component of plasma membranes, are always found on the exterior surface of cells, where they are bound either to proteins (forming glycoproteins) or lipids (forming glycolipids).
  • Glycoproteins embedded in membranes play important roles in cellular identification. They allow interactions with extracellular surfaces to which they must adhere, and they play an important role as part of receptors for many hormones and other chemical communication biomolecules.

Table 3: Summary of the components of the plasma membrane. (Adapted from Rye et al. 2016/Biology/OpenStax)
Component	Location
Phospholipids	Main fabric of the membrane
Cholesterol	Tucked between the hydrophobic tails of the membrane phospholipids
Integral proteins	Embedded in the phospholipid bilayer; may or may not extend through both layers
Peripheral proteins	On the inner or outer surface of the phospholipid bilayer, but not embedded in its hydrophobic core
Carbohydrates	Attached to proteins or lipids on the extracellular side of the membrane (forming glycoproteins and glycolipids)

Key Terms

amphiphilic/amphipathic

molecule possessing a polar or charged area and a nonpolar or uncharged area capable of interacting with both hydrophilic and hydrophobic environments

cell membrane

specialized structure that surrounds the cell and its internal environment; controls movement of substances into/out of cell

fluid mosaic model

describes the structure of the plasma membrane as a mosaic of components including phospholipids, cholesterol, proteins, glycoproteins, and glycolipids (sugar chains attached to proteins or lipids, respectively), resulting in a fluid character (fluidity)

glycocalyx

coating of sugar molecules that surrounds the cell membrane

glycolipid

combination of carbohydrates and lipids

glycoprotein

combination of carbohydrates and proteins

hydrophilic

molecule with the ability to bond with water; “water-loving”

hydrophobic

molecule that does not have the ability to bond with water; “water-fearing”

integral protein

protein integrated into the membrane structure that interacts extensively with the hydrocarbon chains of membrane lipids and often spans the membrane; these proteins can be removed only by the disruption of the membrane by detergents

peripheral protein

protein found at the surface of a plasma membrane either on its exterior or interior side; these proteins can be removed (washed off of the membrane) by a high-salt wash

phospholipid

amphipathic lipid made of glycerol, two fatty acid tails, and a phosphate group

phospholipid bilayer

a biological membrane involving two layers of phospholipids with their tails pointing inward

plasma membrane

a phospholipid bilayer with embedded (integral) or attached (peripheral) proteins that separates the internal contents of the cell from its surrounding environment

saturated fatty acid

long-chain of hydrocarbon with single covalent bonds in the carbon chain; the number of hydrogen atoms attached to the carbon skeleton is maximized

semi-permeable membrane

membrane that allows certain substances to pass through

steroid

type of lipid composed of four fused hydrocarbon rings forming a planar structure

triacylglycerol (also triglyceride)

fat molecule; consists of three fatty acids linked to a glycerol molecule

unsaturated fatty acid

long-chain hydrocarbon that has one or more double bonds in the hydrocarbon chain

X-ray crystallography

an experimental procedure to determine the atomic and molecular structure of a crystal. The crystalline structure causes a beam of X-rays to diffract into many different directions. The angles of the diffracted beams are measured to produce a 3-dimensional image